1531. A CMV Vaccine Based on Non-Replicating Lymphocytic Choriomeningitis Virus Vectors Expressing gB and pp65 Is Safe and Immunogenic in Healthy Volunteers, Allowing for Development of a Phase II Clinical Trial in Living Donor Kidney Transplant Recipients

BACKGROUND: Cytomegalovirus (CMV) is a major pathogen in pregnancy and immunocompromised patients. Antiviral prophylaxis is limited by toxicities, recurrent infection, and antiviral resistance. A safe and protective CMV vaccine is highly desirable. METHODS: HB-101 is a CMV vaccine consisting of two nonreplicating lymphocytic choriomeningitis virus vectors, one expressing the human CMV antigen pp65 and the other a truncated, more antigenic isoform of the CMV fusion protein gB. The safety and immunogenicity of HB-101 were evaluated in a randomized, placebo-controlled, double-blind phase I dose-escalating trial (NCT02798692). Three dosing cohorts (1: 2.6 × 10(6); 2: 2.6 × 10(7) and 3: 2.6 × 10(8) FFU) of 18 subjects each were enrolled. On Day 0, Month 1, and Month 3, HB-101 or placebo was administered to 14 and 4 subjects, respectively. Immunogenicity studies included cellular responses against pp65, and humoral and cellular responses against gB and the LCMV vector. RESULTS: Injection site pain was the most frequently reported solicited adverse event (SAE). It affected 57.1% of HB-101 recipients in both cohorts 1 and 2 and 92.9% in cohort 3. Among the general SAE malaise, fatigue and generalized myalgia were most frequently reported. All SAE were generally mild to moderate and lasted <8 days. No serious adverse events and no abnormal lab tests were noted during the active phase of the study. HB-101-induced gB-specific IgG antibody responses at all doses, in a dose-dependent manner. All three dose levels also induced antibodies that neutralized HCMV infection in cultured human fibroblasts (MRC-5 cells), and resulted in a robust, boosterable and durable T-cell response by IFNγ ELISPOT for CMV gB and pp65. Polychromatic flow cytometry indicated induction of a high proportion of polyfunctional CMV-specific CD8 and CD4 T-cells. CD8 T-cells expressing IFNγ, IL2 and TNFα without CD107a were among the most prominent populations induced against CMV pp65. CONCLUSION: HB-101 is a novel CMV vaccine with a good safety profile in healthy volunteers, eliciting strong humoral and cellular immune responses. We are starting a Phase 2 trial in kidney transplant candidates at higher risk for CMV infection. We plan to give multiple vaccinations prior to living donor kidney transplant, and will follow post-transplant for safety, immunogenicity, and efficacy. DISCLOSURES: C. N. Kotton, Hookipa: Consultant, Consulting fee and Speaker honorarium. M. Schwendinge, Hookipa: Employee, Salary. G. Thiry, Hookipa: Consultant, Consulting fee. B. DeVos, Hookipa: Consultant, Consulting fee. F. De Boever, Hookipa: Consultant, Consulting fee. G. Leroux-Roels, Hookipa: Consultant, Consulting fee. A. Lilja, Hookipa: Employee, Salary.